Effects OF Accidental Antihyperglycemic Overdoses on Lysosomal Enzymology in Patients With Type 2 Diabetes Mellitus

Abstract

Background: Quantitative estimation of lysosomal enzymes in the blood reflect the pathophysiologicalstate of the intracellular lysosomes and subsequently the mother cells. Aim: To assess the effect of inducedhypoglycemia due to accidental intake of antihyperglycemic drugs (insulin and/or sulfonylurea)overdoses by type-2 diabetic patients on some serum lysosomal enzymes. These are reliable markers ofthe intracellular lysosomal bioactivities and long-term cell lifespan. Subjects and Methods: Thirty type-2diabetic patients suffering from severe hypoglycemia because of accidental overdose intake of insulin injection(8 patients), sulfonylurea ingestion (10 cases) or both drugs together (12 patients) due to drug automationand/or missed or disproportionate meal. At the same time, 15 patients with controlled DM, 15patients with uncontrolled DM and 10 healthy reference individuals were studied. All these groups werealmost of matched age, sex and body weight. Blood samples were withdrawn after breakfast and the designatedantihyper-glycemic intake. Beside, plasma glucose, three serum acidic lysosomal enzymes i.e. thecarbohydrase: BN acetyl glucosaminidase (B-NAG), the protease: cathepsin-D (CATH-D) and the monophosphoricester hydrolase: non-prostatic acid phosphatase (NPAP) were determined by the respectivecolorimetric method. Results: Accidental intake of insulin injection and/or oral antihyperglycemic drugsin overdoses induced significant increase of the estimated serum lysosomal enzymes. In this respect, theresponse to insulin was higher but shorter than that by sulfonylurea intoxication. At the same time, BNAGhad higher response than CATH-D and NPAP to the antihyperglycemic drug overdoses. There wasno significant correlation between plasma glucose concentrations and the estimated serum lysosomal enzymeactivities in the different studied groups. The results of the controlled euglycemic diabetics were significantlylower than those in the hypoglycemic group but not significantly different from those in thehealthy group. At the same time, the results of the uncontrolled diabetics were significantly lower thanthose in the hypoglycemic group but significantly higher than the respective values of the healthy reference group. Conclusion: Insulin overdose hypoglycemia in diabetic patients induced a significant increasein libation of the studied lysosomal enzymes (B-NAG, CATH-D and NPAP) more than by sulfonylureatoxicity. On the other hand hyperglycemia in uncontrolled diabetics induced significantly higherserum lysosomal enzymes than normal but significantly lower than those in hypoglycemics. Serum lysosomalenzymes profile is a mirror of the intracellular lysosomal biological state and consequently the celllife span.